Neurotoxicity from glutathione depletion is dependent on extracellular trace copper.
作者： Anthony R. White , Roberto Cappai
DOI: 10.1002/JNR.10537
关键词: Neurotoxicity 、 Extracellular 、 Oxidative stress 、 Buthionine sulfoximine 、 Neurodegeneration 、 Intracellular 、 Glutathione 、 Chemistry 、 Biochemistry 、 Antioxidant
摘要: Glutathione (GSH) is an important antioxidant, and its depletion in neurons has been implicated several neurodegenerative disorders. Aberrant copper metabolism also neurodegeneration may result the generation of toxic free radicals. However, little known about relationship between GSH homeostasis. In present study, we examined role extracellular trace biometals neuronal cell death induced by depletion. Treatment primary cortical with buthionine sulfoximine (BSO), inhibitor synthesis, a rapid loss intracellular GSH, leading to decreased viability. Neuronal was dependent on levels culture medium (1.6 μM). Neurons were protected against depletion-mediated toxicity when cultured Chelex 100-treated containing tenfold less (0.16 μM) than normal medium. The addition copper, but not iron or zinc, restored neurotoxicity Moreover, BSO inhibited chelators. neurotoxic effects GSH-depleted involved copper(I) subsequent radical-mediated oxidative stress. These studies demonstrate critical for caused have implications understanding processes diseases. © 2003 Wiley-Liss, Inc.
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